From Mendel to Biotechnology: A Critical Look at the Historical Development and Philosophical Foundations of Modern Biology

In retrospect, the sixth decade of the nineteenth century was truly remarkable with respect to the development of the science of biology. By the end of those ten years all of the pieces were in place for the maturation of what had been a purely observational discipline into one with a strong theoretical basis. The key elements of what would become modern biology had been discovered and formulated. However, it took more than eighty years to bring all of them together (1). The result, the field of molecular biology and its attendant sub-disciplines, is grounded philosophically in a mechanistic, deterministic and reductionist view that derives from the logical empiricist setting in which it was born and which has not changed, despite the radical shift that has come about in the physical sciences.

November 1859 saw the first publication of Charles Darwin's On the Origin of Species, describing his theory of evolution based upon data gathered during his voyages on the H.M.S. Beagle. At this same time Fr. Gregor Mendel, an Augustinian monk in Brünn, Austria, was already in the middle of his experiments with breeding patterns of the common garden pea. This work would lead to his publication, in 1866, of the two laws of genetics and his conceptualization of the gene as the unit of inheritance. By 1869, the chemist Johann Friedrich Miescher, working with used bandages obtained from a hospital caring for the wounded of the Crimean War, had isolated from human pus the substance he called nuclein, which soon after began to be called nucleic acid. The journey to the future of biology had begun.

At the time of those events, biology could hardly be compared to the so-called "hard" sciences such as physics, chemistry or astronomy, all of which rested upon strong theoretical platforms, mainly derived from Newton. Biology had essentially been an exercise in observation and classification, the only major developments being more refined systems for organizing the various species. With Darwin's theory and Mendel's laws, biology had for the first time a potential theoretical basis of its own.

The publication of On the Origin of Species in late 1859 put forth the argument that Darwin and, independently, Alfred Wallace, had been making that species evolved and that the pressure or driving force of this evolution was natural selection or the fitness of the individual for the environment. Darwin inferred speciation without being able to observe it, given the geological time necessary for such changes to become fixed in a population. Nevertheless, his theory was supported by such evidence as the fossil record and his observations of geographic distribution of species and unique evolutionary niches such as the Galapagos Islands. Despite the strength of the theory for explaining the development of the diversity of life, it lacked any idea about how natural selection would act to drive the process.

Gregor Mendel had received excellent training in both physics and chemistry at the University of Vienna. In addition, the monastery in Brünn was a center for scientific study, with his brother monks being specialists in all of the disciplines. As a consequence, Mendel found himself in the midst of a veritable cauldron of investigation. His work on the breeding patterns of the pea had been stimulated by earlier results of botanists who had observed the products of crossing plants with different traits. Mendel brought to this work a tool the others had lacked, quantitation. It was through a painstaking gathering of data from hundreds of crosses of his plants that Mendel was finally able to deduce what he called the First and Second Laws of Heredity. Along the way he formulated a simple model by which these laws could operate and proposed that observed traits are determined by discrete "factors," now called genes.

Mendel's work, published in the Proceedings of the Brünn Society for Natural History, was all but ignored by his contemporaries. Years later, copies of his paper were found unopened among the papers of some prominent biologists. It was not until 1902 when three experimenters, working independently, rediscovered the principles formulated by Mendel. Each of them, Hugo de Vries, Carl Correns and Erich von Tschermak, cited Mendel's 1866 paper, and the branch of biology known as genetics was launched. Through the work of scientists such as Thomas Hunt Morgan and his student Alfred Sturtevant, the theory of how genes are inherited took firm shape. The nature of the genetic material, however, remained to be discovered.

The isolation of what was essentially deoxyribonucleic acid (DNA) from the white cells in human pus and later from salmon sperm had been reported by Miescher and gone unnoticed. DNA was later shown to be a component of structures called chromosomes, found in the nucleus of cells and which behave during cell division just as one would predict for the "factors" or genes of Mendel. These chromosomes also contained substantial amounts of protein, a fact which would confuse and confound biologists for another half-century.

At this point it should be stated that interest in the gene was coming from different directions. Geneticists were, of course, concerned with determining what genes do and how they behave. Chemists who approached this topic were interested in the substance of which genes are made. Physicists, interestingly enough, were stimulated to think of how it could be that genes exist. And, in the background, evolutionists were considering that genes might in fact be the things upon which natural selection acts.

Concern about the chemical nature of the gene focused on the two components of the chromosome, the cellular structure shown by Morgan and his collaborators to be the physical location of genes. Proteins were known to be complex macromolecules, consisting of 20 different amino acids, and showing a wide diversity of composition. DNA, on the other hand, was thought to be quite simple, according to the work of the chemist Phoebus A. Levene. From his analysis these large molecules contained equal amounts of each of the four nitrogenous bases, adenine (A), guanine (G), cytosine (C) and thymine (T). It was not until the improved techniques developed by Erwin Chargaff in the late 1940's that the detailed composition of DNA was revealed to be quite complex and to differ dramatically depending upon the organism from which it is isolated.

The work of Oswald Avery and his collaborators Colin McLeod and Maclyn MacCarty at Rockefeller University led to their publication, in 1944, of evidence that a DNA component of certain bacteria was the material responsible for the genetic phenomenon of transformation. This work did not have the immediate impact and importance it would later receive, in part due to the prevailing acceptance of Levene's DNA structure.

It is at this point that the influence of physics is directly seen in subsequent developments. Erwin Schrödinger published, in 1944, a small book called What is Life? in which he challenged physicists to examine the structure of these things called genes (2). He believed that their stability of structure during transmission from generation to generation might imply the existence of some unknown principles of energetics. One young physicist who responded to this challenge was Max Delbrück. He became, along with Salvador Luria and Gunther Stent, a major part of the driving spirit behind the development of the new science of molecular biology.

Delbrück and his colleagues were called the Phage Group, after their experimental organism of choice, the bacterial viruses or bacteriophage of E. coli (3). In spite of Schrödinger's challenge no new physical principles were discovered. But it was out of the efforts of this group that the experiment of Alfred Hershey and Martha Chase arose, supporting the notion that DNA is the genetic material. And it was from the related efforts generated by this demonstration that the X-ray crystallographic work of Rosalind Franklin and Maurice Wilkins would lead to the model proposed by James Watson and Francis Crick in 1953. The model accounted for the structure of a gene in the sequences of the bases (A, G, C and T), the pattern of replication which distributed these genes to offspring and the ability of changes in the base sequence to result in mutations or alterations to the gene in question. The pathway to the modern era, including all of the biotechnology industry and the Human Genome Project, was now open for travel.

Waiting in the wings for these developments were the ideas of Darwin. Here at last was the missing information. It would have been the genes and, more specifically, the DNA itself, upon which natural selection acted. Mutations in the gene, identified as changes in the sequence of bases in the DNA, would lead to different genetic traits that could be selected for or against by changes in the environment. As a result, the neo-Darwinists had not only an answer to the original problem but a firm grounding in the new theoretical structure of biology. Now the theory of evolution and the laws of genetics were intertwined by a common thread, both literally and figuratively, in the form of DNA.

Thomas Kuhn has characterized the progress of science as a series of "revolutions" resulting in what are sometimes dramatic shifts in the paradigm agreed upon by the community representing the discipline (4). In Table 1 I list three of the shifts that occurred in the development of modern molecular biology.

The result of the acceptance and establishment of these ideas is that modern biology has matured into a science with a theoretical foundation. It must be noted that the philosophical basis for this foundation derives from the Humean call for reductionism as well as from Cartesian/Newtonian mechanistic determinism. These underlying suppositions have remained essentially unchanged in spite of the new world view brought about by quantum theory in physics and by the efforts of the systematists to change the orientation of biology to a more holistic position. As a result, a good deal of modern biology is concerned with the identification of genes as the prime explanation for the biology of the organism. From this derives the impetus behind the Human Genome Project and much of the molecular approach to medical treatment. The current paradigm is reductionist and, in its extreme application as represented by workers such as Richard Dawkins (5), champions genetic determinism.

It is clear that modern biology has had great success in representing the reality of living systems in a form that yields a great deal of both theoretical and practical information. Our understanding of all of the mechanisms by which these macromolecules act and interact as a part of the life functions of an organism derive from this paradigm and the techniques it has produced. And yet, there are clearly aspects of living systems, especially in the case of our own species, that have not yielded to this analysis. Among these features are included the organization of the human brain and, more importantly, the origin of the mind and of consciousness. It has become increasingly difficult to model these kinds of natural phenomenon in terms of the reductionist paradigm extant in much of biological thinking.

A major part of the difficulty appears to be the framework within which the natural world is viewed in modern biology. As an inheritor of the logical empiricists' position, the biologist believes that the only aspects of the world that are observable and, in fact, relevant are those which would be, in Aristotelian terms, material cause and formal cause. In addition, as a strict Cartesian, the biologist holds to the complete duality of mind and body.

Modern biology does not recognize nor does it incorporate into theoretical considerations either the efficient or final cause of a thing. The idea of teleological thinking is viewed as a slur when applied to any kind of biological model or conclusion. Nonetheless, purpose and plan are obvious in living systems, especially in the case of humans. Some time ago Francisco Ayala pointed out three types of teleological explanations that are appropriate to biological systems: a) conscious anticipation of an end-state or goal, b) self-regulating systems and c) structures designed to perform a specific function (6). Indeed, when a student asks the purpose for which a cell undergoes the process of mitosis, the answer given is a teleological one ("in order to produce two daughter cells with the same genetic composition as the parent cell'). This hypocritical view is, I believe, the direct result of the structure of the scientific enterprise that biology has inherited from the nineteenth century empiricists.

The philosophical stance which many modern biologists take, either knowingly or unaware, can lead to serious errors in logic, especially when there is an attempt made to extend the results of the science into areas that are outside of the domain of science. An example is the view, held by certain neo-Darwinists such as Dawkins and Daniel Dennett, that the results of evolutionary theory combined with genetics and molecular biology serve to eliminate all thought of a Creator. The result is what Pope John Paul II has called "metascientific concepts" (7). In Table 2, I describe the steps that have taken place in the formulation of the modern concept of Darwinian evolution and how that formulation has led some scientists into metascientific fallacies.

This state of affairs is exemplified by the quote from Dennett:

"A familiar diagnosis of the danger of Darwin's idea is that it pulls the rug out from under the best argument for the existence of God that any theologian or philosopher has ever devised: the Argument from Design. What else could account for the fantastic and ingenious design to be found in nature? It must be the work of a supremely intelligent God. Like most arguments that depend on a rhetorical question, this isn't rock-solid, by any stretch of the imagination, but it was remarkably persuasive until Darwin proposed a modest answer to the rhetorical question: natural selection. Religion has never been the same since. At least in the eyes of academics, science has won and religion lost. Darwin's idea has banished the Book of Genesis to the limbo of quaint mythology. (8)"

The problem here is that a science which embraces Hume's assertion that the efficient and final causes of a thing can never be known is trying to "prove" the non-existence of the Uncaused Cause. A key misunderstanding that is immediately evident in this chain of reasoning is the nature of chance or random events. The neo-Darwinist assumes that the random nature of mutational changes in DNA eliminates causality from the consideration. In fact, the mechanisms of mutation are well understood and proceed by quite specific steps, even though the "chance" of a particular base being mutated at a given time in a given organism is probabilistic. The overall result can be seen as having both an efficient cause (e.g., the agent of mutation) and a final cause (e.g., the consequence of the mutated gene on the function of the organism). Although the biologist cannot predict which gene will be changed in a particular organism, the dependence of the functioning of that organism on that change can be observed.

The interpretations of quantum theory have lead to a number of philosophical issues, among which are the paradoxes that arise from a consideration of the outcomes on this view of reality. The "Schrödinger's cat" conundrum is a classic of this venue. The issue for the physicist is the ambiguous state of the cat before the box is opened and the experiment is observed. The issue for the biologist begins, however, when the box is opened.

Let us assume, for argument, that the vial of poison present in the famous box contains cyanide, and that when the random event of radioactive decay occurs, the vial is broken and the cat inhales the gas. When the experiment is observed (i.e., the box is opened) and the cat is found to be in the state termed "dead," a biochemical analysis would reveal that the cytochrome oxidase molecules present in the mitochondrial membranes of the cat were all inactivated by the cyanide. In fact, if we could have gotten to the cat soon enough, we might have administered an antidote which could have reversed this inactivation, thus saving the animal's life. The biological paradox, however, is that the difference between the cat in state "dead" and the cat in state "alive" is more than just a functioning cytochrome oxidase. We cannot simply assemble a cat from all of the molecular components, including the functioning enzyme systems and genetic information. I do not argue here for a return to the out-moded concept of vitalism. Rather, it seems that biology needs an acceptance of the view that living systems have properties that emerge from the unique interactions of their components in ways that may even be predictable from the properties of the components themselves (9).

Modern biology cannot definitively answer the question "What is the difference between the state of the cat in the two possible outcomes of the experiment." What is the difference between Schrödinger's cat alive or dead? Until the philosophical structure of the discipline allows for features of the natural world such as emergent properties, efficient and final causes and the possibility of explanations that may even include metaphysics, biology will be unable to answer Schrödinger's question. The biologist cannot determine what "life" really is.

References

1. For a comprehensive review of the history of the development of modern biology, see the most recent edition of "The Eighth Day of Creation" by Horace F. Judson, Cold Spring Harbor Press, New York, 1996.

2. Erwin Schrödinger, "What is Life," Cambridge University Press, Cambridge, England, 1944.

3. The history of the early years of molecular biology is told in a book originally published in 1966 as a "festschrift" for Max Delbrück. The most current edition of this work is "Phage and the Origins of Molecular Biology," edited by John Cairns, Gunther Stent and James Watson, Cold Spring Harbor Press, New York, 1992.

4. Thomas S. Kuhn, "The Structure of Scientific Revolutions" 3rd Edition, The University of Chicago Press, 1996.

5. Richard Dawkins, "The Selfish Gene," Oxford University Press, Oxford, England, 1989.

6. Francisco J. Ayala, "Teleological Explanations in Evolutionary Biology" in Philosophy of Science, (1970), v. 37, pp. 1-15.

7. Pope John Paul II, "Lessons of the Galileo Case," Origins, (1992),v. 22, p. 371.

8. Daniel Dennett, quoted in John Brockman, "The Third Culture," Simon and Schuster, New York, 1995, p. 187

9. Stuart Kauffman, "The Origins of Order," Oxford University Press, New York, 1993.